Keraderm LLC and the Wellman Center for Phototherapy propose a radically new treatment for onychomycosis using germicidal radiation instead of current medications which have significant drawbacks. Onychomycosis is a fungal nail infection that affects approximately 30 million Americans. Americans spend more than $1 Billion per year to treat this problem. However, this number does not represent the true magnitude of the problem since many people do not seek treatment due to the drawbacks of currently available treatments. The current treatments of choice for onychomycosis are oral medications- the best of which have a total cure rate of less than 40%, are expensive (in the range of $1,000), and have serious side effects including heart and liver problems and in some instances death. This application seeks to develop a completely novel therapy for onychomycosis; the application of germicidal UV radiation (UVC). Limited testing at Keraderm and Wellman indicates that UVC phototherapy can successfully treat onychomycosis in patients. We propose to determine why UVC is efficacious and lay the foundation to develop a non-invasive, safe, and highly efficacious treatment for onychomycosis. The application has five aims: 1) Construct dose-response curves for UVC inactivation of the organisms often responsible for onychomycosis -T. rubrum, T. mentagrophytes, and Epidermophyton floccosum. 2) Determine the transmissivity of the human nail with respect to UVC to determine the proper dose of UVC. 3) Investigate the mechanism of fungal death. 4) Determine whether dermatophytes can develop resistance to UVC by repeated cycles of sub-total killing and re-growth. 5) Determine the possible side effects of UVC on keratinocytes that may be exposed during UVC irradiation of infected toenails. The Phase 2 application will use information collected during Phase 1 to design clinical trials to develop a treatment that will provide a low cost, safe, and effective treatment for the estimated thirty million Americans who are afflicted with onychomycosis. Keraderm believes the current market of more than $1 Billion per year will significantly expand once a safe, effective, and low cost treatment is available since the majority of currently affected persons do not seek treatment due to the drawbacks associated with current therapies. [unreadable] [unreadable] [unreadable]